Handheld pipette and pipetting method

Abstract

The application relates to a handheld pipette, comprising a handheld part, a pipette tip at one end of the handheld part, the pipette tip being formed with a liquid storage cavity for containing liquid; the liquid storage cavity is provided with a special ultrasonic device in the liquid storage cavity or on the inner wall of the liquid storage cavity; the liquid outlet comprises a through hole, the size of the through hole is limited so that the liquid in the liquid storage cavity does not flow out of the through hole when the special ultrasonic device is not working; when the special ultrasonic device is in a working state, the liquid in the liquid storage cavity is driven to generate a sound beam flow towards the through hole, at least part of the sound beam flow is emitted through the through hole to form a liquid drop. A pipetting method is also provided. The application can realize accurate micro pipetting, the size of the pipetting liquid drop can reach the order of picoliter to nanoliter, and the stability of the ejected liquid drop and the uniformity of the size are maintained.

Description

Technical Field

[0001] This application relates to the fields of automated liquid handling technology and microfluidics technology, and in particular to a handheld pipette and a pipetting method. Background Technology

[0002] Handheld pipettes are commonly used instruments in production and laboratories. Conventional handheld pipettes have a piston-type structure. By operating the piston, it moves up and down within the piston chamber, allowing the pipette tip connected to the piston chamber to pick up and discharge liquid.

[0003] Pipettes with piston-type structures offer poor droplet control, while precise micro-pipetting is a crucial aspect of scientific research, production, and testing in fields such as biology, chemistry, and medicine. Therefore, developing a pipette capable of achieving precise micro-pipetting remains a challenging technical problem. Summary of the Invention

[0004] This application provides a handheld pipette and a pipetting method, which enables precise micro-pipetting.

[0005] To achieve the above objectives, a first aspect of this application provides a handheld pipette, comprising: a handheld portion and a pipette tip located at one end of the handheld portion, the pipette tip forming a liquid reservoir; the liquid reservoir having an outlet and an inlet, and an ultrasonic device disposed within or on the inner wall of the liquid reservoir; the outlet including a through hole, the size of which is limited so that liquid in the liquid reservoir does not flow out of the through hole when the ultrasonic device is not in operation; when the ultrasonic device is in operation, it drives the liquid in the liquid reservoir to generate an acoustic beam toward the through hole, at least a portion of the acoustic beam being ejected through the through hole to form droplets.

[0006] In some feasible embodiments, the distance between the ultrasonic device and the through-hole is set such that the energy of the ultrasonic device can be completely attenuated and converted into the energy of the droplet jet.

[0007] In some feasible embodiments, the ultrasonic device is positioned directly opposite the through-hole.

[0008] In some feasible implementations, the through-holes are arranged in an array of multiple, and the ultrasonic devices are correspondingly multiple.

[0009] In some feasible embodiments, the pipette tip is generally trapezoidal in shape, with the bottom of the trapezoidal shape connected to the handheld part, the top of the trapezoidal shape having the through hole, the side of the trapezoidal shape having the liquid inlet, and the interior of the trapezoidal shape forming the liquid storage cavity communicating with the through hole and the liquid inlet.

[0010] In some feasible embodiments, the height of the inlet is higher than that of the ultrasonic device, so that the space between the ultrasonic device and the through-hole is filled with the liquid.

[0011] In some possible implementations, at least one of the following is also included: at least one button located on the surface of the handheld portion for controlling the operating state of the ultrasonic device, adjusting the drive signal or power of the drive device of the ultrasonic device; a hook located on the side of the handheld portion away from the pipette tip; the drive device of the ultrasonic device built into the handheld portion; or, the drive device of the ultrasonic device externally placed on the handheld portion, and a cable passing through the handheld portion and electrically connecting the ultrasonic device and the drive device.

[0012] The second aspect of this application provides a pipetting method using any of the handheld pipettes described in the first aspect. The method includes: injecting liquid into the reservoir of the pipette through the inlet; orienting the pipette tip toward a target position; activating an ultrasonic device to generate an acoustic beam in the liquid of the reservoir toward a through-hole, wherein at least a portion of the acoustic beam is ejected through the through-hole to form a droplet and reach the target position.

[0013] In some feasible ways, the method also includes adjusting the drive signal or power of the drive device of the ultrasonic device to change the size of the droplet.

[0014] In some possible implementations, the drive signal of the drive device for adjusting the ultrasonic device includes at least one of the following: adjusting the duty cycle of the drive signal, the duration of the continuous period of the drive signal, and the waveform.

[0015] In some possible implementations, this also includes: suspending the ultrasonic device and directing the pipette tip toward another target location.

[0016] The technical solution provided in this application achieves precise micro-volume pipetting by driving liquids with ultrasonic waves. Not only are the droplet sizes small, ranging from picoliters to nanoliters, but the stability and size uniformity of the ejected droplets are also maintained. Furthermore, this application can control the size of the generated droplets by varying the driving signal of the ultrasonic device, thus changing the droplet resolution (i.e., size) to suit different needs.

[0017] On the other hand, this application is based on ultrasonic-driven liquid, directly acting on a local liquid (the ultrasonic device is directly facing the liquid where the sound beam is generated) to generate a sound beam. This is completely different from existing ultrasonic-based principles (for example, see Chinese Patent Publication No. CN220610445U). The ultrasonic frequency is much lower than that of ultrasonic waves and does not generate a sound beam. The ultrasonic waves mainly cause the liquid to contract and oscillate or produce a cavitation effect, which is then conducted to the surface of the liquid outlet to generate droplets. This method has low efficiency (e.g., low energy conversion rate) and poor controllability (droplet size stability). In contrast, this application has stronger controllability, better maintains the stability and size uniformity of the ejected droplets, and has relatively higher efficiency. Attached Figure Description

[0018] Figure 1 This is a circuit diagram of a special ultrasonic device driving device;

[0019] Figure 2 Is using Figure 1 The schematic diagram of the circuit that generates a driving signal:

[0020] Figure 3 Is using Figure 1 The schematic diagram of the circuit that generates another driving signal;

[0021] Figure 4 This is a schematic diagram of a handheld pipette provided in an embodiment of this application;

[0022] Figure 5 This is a cross-sectional schematic diagram of the pipette tip provided in an embodiment of this application;

[0023] Figure 6 This is a schematic diagram of three special ultrasonic devices with a common substrate and electrodes provided in the embodiments of this application;

[0024] Figure 7 This is a schematic diagram of the liquid storage chamber and through hole provided in an embodiment of this application;

[0025] Figure 8 This is a schematic diagram showing the dimensions of the ultrasonic device, which is an integrated acoustic resonator, provided in the embodiments of this application.

[0026] Figure 9 A schematic diagram of the circuit principle of a handheld pipette provided in an embodiment of this application;

[0027] Figure 10 An experimental photograph and result diagram provided for an embodiment of this application;

[0028] Figure 11 An experimental data graph provided for an embodiment of this application.

[0029] It should be understood that the dimensions and shapes of the blocks in the above structural diagrams are for reference only and should not constitute an exclusive interpretation of the embodiments of the present invention. The relative positions and inclusion relationships between the blocks presented in the structural diagrams are only schematic representations of the structural relationships between the blocks, and are not intended to limit the physical connection methods of the embodiments of the present invention. Detailed Implementation

[0030] The technical solutions provided in this application will be further described below with reference to the accompanying drawings and embodiments. It should be understood that the system architecture and business scenarios provided in the embodiments of this application are mainly for illustrating possible implementations of the technical solutions of this application and should not be construed as the sole limitation on the technical solutions of this application. Those skilled in the art will recognize that the technical solutions provided in this application are equally applicable to similar technical problems as system architectures evolve and new business scenarios emerge.

[0031] It should be understood that the droplet ejection solutions provided in this application include handheld pipettes, pipetting methods, and related applications. Since these technical solutions solve problems based on the same or similar principles, some repetitions may not be repeated in the following descriptions of specific embodiments. However, these specific embodiments should be considered as mutually referencing each other and can be combined with each other.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In case of any inconsistency, the meaning set forth in this specification or derived from the content described herein shall prevail. Furthermore, the terminology used herein is for the purpose of describing embodiments of this application only and is not intended to limit this application. To accurately describe the technical content of this application and to accurately understand the invention, the following explanations or definitions of the terms used in this specification are provided before describing specific embodiments:

[0033] 1) High-frequency resonator: This can be a device that generates mechanical vibration by applying voltage based on the piezoelectric effect. In this application, a piezoelectric resonator that generates ultrasonic waves of not less than 0.5 GHz (GHz is equivalent to gigahertz) during operation is used. Preferably, it is a piezoelectric resonator that generates ultrasonic waves of not less than 1 GHz and not more than 30 GHz during operation, for example, it can be 2 GHz to 2.5 GHz. Such piezoelectric resonators can be, for example, surface acoustic wave (SAW) devices, bulk acoustic wave (BAW) devices, etc. For example, when it is BAW, it can be a thin-film bulk acoustic wave resonator (FBAR), a solid-state assembled resonator (SMR), or a Lamb wave resonator (LWR). For ease of description, the piezoelectric resonator that can generate ultrasonic waves of not less than 0.5 GHz will be referred to as an ultrasonic device below.

[0034] 2) Several effects of ultrasonic devices acting on liquids.

[0035] Ultrasonic devices, when applied to liquids (or liquids with environmental boundaries) within a flow channel, can generate jet effects (propelling the liquid in a straight line), secondary flow effects (such as eddies caused by local circulation generated by the jet, also known as micro-vortices), and acoustic beam effects (propelling the liquid in a highly focused, high-speed straight line). For a detailed description of jet, secondary flow, and acoustic beam effects, please refer to Chinese patent application number CN202410832207.9.

[0036] Ultrasonic devices, when applied to liquids with unrestricted surfaces, can produce droplet ejection (forming droplets that break through the liquid surface or a continuous column of droplets) and atomization (forming a mist that breaks through the liquid surface) effects when the liquid level is below a certain height. The basic principles of droplet ejection and atomization are similar. However, with the same driving signal from the ultrasonic device, the required liquid level for atomization is lower than that for droplet ejection. Here, liquid level refers to the distance between the working surface of the ultrasonic device and the liquid surface. When the liquid level is greater than the height at which the sound wave completely attenuates, the sound wave energy can be fully utilized to drive the liquid to generate droplets.

[0037] 3) Signal duration within a driving cycle: In this application, electrical energy can be applied to the ultrasonic device continuously or intermittently to drive the ultrasonic device.

[0038] When using intermittent loading, please refer to... Figure 2 As shown, during the power-on phase of the switching power supply (corresponding to...) Figure 2 The high-level switch signal represents the duration of the signal within the drive cycle, also known as the first stage of the drive cycle. Corresponding to the output signal of the drive unit, several signals will be output during this duration. For example, when the signal generator outputs a 1GHz signal, assuming the first stage lasts for 1 microsecond, the drive unit will output 1000 signals during this first stage. The power applied during the first stage will be applied to these 1000 signals. The stage during which no drive signal is output within the drive cycle is the second stage, which also corresponds to the power supply off stage (corresponding to...). Figure 2 (Switch signal low level).

[0039] In certain cases, such as when the first phase is executed only once and then ends, this is equivalent to, or considered as, executing only one drive cycle, and therefore this situation is also within the scope of protection of this application.

[0040] For example, when the first stage accounts for 100% of the driving cycle (i.e., the duration of the second stage is 0), that is, the driving unit continuously outputs several signals, which is the continuous loading of electrical energy as described in this application, this situation is also within the scope of protection of this application.

[0041] 4) Driving device for special ultrasonic devices: such as Figure 1 One embodiment is shown, including a control unit and a drive unit, the drive unit comprising a signal generator and a power amplifier. Its signal output principle can be found in [reference needed]. Figure 3 As shown.

[0042] The signal generator is used to generate high-frequency signals. The frequency of the original high-frequency signal it generates is the same as or approximately the operating frequency (or natural frequency) of the ultrasonic device used as a load. The waveform of the signal generator can be a rectangular wave (e.g.,...). Figure 3 The signals shown include square waves, sawtooth waves, sharp pulses (or triangular waves), stepped waves, sine waves, or half-waves. The output signal of the corresponding drive unit is modulated into sawtooth waves, sharp pulses (or triangular waves), stepped waves, sine waves, or half-waves.

[0043] A power amplifier is used to amplify the signal to be output so that it can drive a high-performance ultrasonic device.

[0044] The control unit can be a switching power supply, which controls the output switching signal. This switching signal can be a periodic signal, with a high level corresponding to the switching on phase (such as the conduction phase of the switching power supply's switching transistor). Figure 3 In the first stage, the switch-off stage corresponds to a low level, which is... Figure 3 The second stage involves controlling the operating voltage or amplification factor input to the power amplifier to achieve different output powers, which is the first power mentioned above. The first power can also be understood as the average energy density input to the ultrasonic device during one drive cycle (which consists of a first stage and a second stage). Since the energy level is related to power and time, the amount of energy input to the ultrasonic device during one drive cycle is related to the level of the first power, the duration of the first stage, or its duty cycle.

[0045] 5) Pulsed Acoustic Beam. When the driving device of the ultrasonic device outputs signals for each driving cycle (hereinafter referred to as driving signals), due to the viscous properties of the liquid itself, when the second stage duration is short, below a certain duration, the acoustic beam may still exhibit continuous characteristics. When the second stage exceeds a certain duration (for example, the second stage accounts for 50%, 70%, etc.), the acoustic beam will exhibit obvious interval characteristics. In this embodiment, the acoustic beam with obvious interval characteristics is referred to as a pulsed acoustic beam. Pulsed acoustic beams are easier to quantitatively control or apply to metrology, etc.

[0046] 6) Positive and negative correlations between parameters: Taking two parameters as an example, positive correlation means that one parameter increases as the other parameter increases, and negative correlation means that one parameter increases as the other parameter decreases. The parameters mentioned in this application cannot be infinitely small or infinitely large. Therefore, unless otherwise specified, the parameter values ​​mentioned in this application refer to values ​​within a reasonable range. For example, when describing a positive correlation between parameter A and parameter B, it means that within a certain range, parameter A and parameter B are positively correlated, and it can be predicted that beyond this range, parameter B will no longer be positively correlated with parameter A (for example, if parameter A increases by a certain value and B reaches a saturation point, then parameter B will no longer increase with the increase of parameter A). This range of values ​​is then considered a reasonable range.

[0047] This application provides a handheld pipette that utilizes an ultrasonic device to generate an acoustic beam within the pipette's reservoir. This beam is then ejected through a through-hole to form droplets at the target location. Due to the high controllability of the ultrasonic device and the strong directional nature of the generated acoustic beam, precise micro-volume pipetting can be achieved. Furthermore, this application's solution maintains the stability and size uniformity of the pipette droplets while keeping the ultrasonic device's drive signal constant. On the other hand, this application can also control the size of the generated droplets by varying the control of the ultrasonic device's drive signal. The following detailed description of this application's solution, in conjunction with the accompanying drawings and embodiments, further illustrates this application.

[0048] The first embodiment of this application provides a handheld pipette, such as Figure 4 and Figure 5 As shown, the handheld pipette includes:

[0049] The handheld part and the pipette tip located at one end of the handheld part, wherein the pipette tip forms a reservoir for containing liquid;

[0050] The liquid storage chamber has an outlet and an inlet, and an ultrasonic device is disposed within the liquid storage chamber or on the inner wall of the liquid storage chamber; such as Figure 5 As shown, the inner wall of the liquid storage chamber forms a support part opposite to the liquid outlet to install the ultrasonic device;

[0051] The liquid outlet includes a through hole, the size of which is limited so that the liquid in the storage chamber does not flow out of the through hole when the ultrasonic device is not working;

[0052] When the ultrasonic device is in operation, it drives the liquid in the reservoir to generate an acoustic beam toward the through hole, and at least a portion of the acoustic beam is ejected through the through hole to form droplets.

[0053] In some embodiments, the inlet of the liquid storage chamber is higher than the outlet, preferably higher than the height of the liquid storage chamber or higher than the height of the ultrasonic device. This ensures that the space between the ultrasonic device and the through hole in the liquid storage chamber is filled with liquid, thereby maintaining the consistency of the liquid level height between the ultrasonic device and the through hole. Furthermore, the setting of the outlet through hole also maintains the relative stability of the liquid level at the through hole. All of these factors contribute to the uniformity of the generated droplet size.

[0054] In some embodiments, a second liquid storage chamber may exist between the liquid storage chamber and the liquid inlet to increase the liquid storage capacity. The second liquid storage chamber may be higher than the first liquid storage chamber below it (the first liquid storage chamber refers to the aforementioned liquid storage chamber with the ultrasonic device and the liquid outlet), and may be connected to the first liquid storage chamber. In some embodiments, the second liquid storage chamber may be located on the side of the first liquid storage chamber opposite to the liquid outlet, for example... Figure 5 The support shown is located on the side opposite the liquid outlet. The second liquid storage chamber can be annular, cylindrical, or similar in shape.

[0055] In some embodiments, the second reservoir may be independently disposed and detachably externally located on the outside of the handle of the handheld pipette. The outlet of the second reservoir may communicate with the inlet of the first reservoir, or the outlet of the second reservoir may extend into the inlet of the first reservoir. For example, the second reservoir may have a locking portion (such as a semi-annular clip) that is detachably locked onto the outer wall of the handle. In some embodiments, the second reservoir may be, for example, in the form of a syringe.

[0056] In some embodiments, the second liquid storage chamber may contain a microporous material, such as microporous ceramics or sponge, which can not only replenish the liquid to the first liquid storage chamber below it, but also has a certain ability to retain and store liquid through the microporous material, which can reduce the possibility that the liquid in the first liquid storage chamber will overflow from the through hole due to excessive liquid storage and high liquid level caused by the addition of the second liquid storage chamber.

[0057] The size of the through-hole is limited to 5 micrometers to 5 millimeters. Based on the surface tension of the droplet at the through-hole, the liquid in the reservoir does not flow out from the through-hole when the ultrasonic device is not in operation.

[0058] In some embodiments, the reservoir is flat, that is, when the handheld pipette is placed vertically, the liquid surface thickness in the height direction is small, for example, less than 2 mm. This results in less pressure exerted by the liquid in the reservoir on the through hole, making it easier to prevent the liquid in the reservoir from flowing out of the through hole.

[0059] On the other hand, when the size of the through hole is smaller than the corresponding liquid column cross-sectional size of the acoustic beam, the through hole can also be used to constrain the amount of acoustic beam passing through the through hole, thereby constraining the size of the droplets formed by the acoustic beam exiting through the through hole, so as to achieve a smaller micro-displacement. The size of the droplets generated by this application can reach the picoliter to nanoliter level.

[0060] In some embodiments, the distance between the ultrasonic device and the through-hole is set such that the energy of the ultrasonic device can be completely attenuated and converted into the energy of droplet ejection. In some embodiments, the distance between the ultrasonic device and the through-hole, that is, the thickness of the liquid from the ultrasonic device to the through-hole, is within a threshold range of 5 micrometers to 2 mm, thus avoiding the atomization effect caused by excessive thickness and also avoiding the inability to eject liquid due to excessive thickness.

[0061] In some embodiments, the ultrasonic device is positioned directly opposite the through-hole. For example, when the ultrasonic device is a BAW (Brainwave Ultrasonic Device), it can be placed inside the reservoir directly opposite the through-hole.

[0062] In some embodiments, the through-holes are arranged in an array of multiple arrays, and the ultrasonic devices are correspondingly multiple arrays. This allows for the formation of multi-channel pipetting.

[0063] In some embodiments, the ultrasonic devices are multiple corresponding devices, meaning there can be multiple independent ultrasonic devices (each with its own substrate and ultrasonic chip). In other embodiments, it can mean at least two ultrasonic chips located on the same substrate and arranged in an array, the at least two ultrasonic chips sharing electrodes on the substrate. This type of integration can reduce wires and reduce energy loss due to line resistance, etc. Figure 6 An example is shown in which a substrate has three ultrasonic chips (here, ultrasonic chips refer to the acoustic wave reflecting layer and piezoelectric layer located on the substrate). The upper electrodes of the piezoelectric layers of the three ultrasonic chips are connected to the same endpoint on the substrate, and the lower electrodes are also arranged to the same endpoint. These two endpoints are used for external driving circuits. Figure 6 The three claw-shaped parts are electrodes, and the rectangular frame is the endpoint (gold finger).

[0064] In some embodiments, there are multiple liquid storage chambers, such as multiple chambers arranged in parallel, each liquid storage chamber having one or more arrayed through holes, and correspondingly having a specific ultrasonic device. When there are multiple liquid storage chambers, batch simultaneous liquid transfer can be achieved.

[0065] In some embodiments, the pipette tip is generally trapezoidal in shape, with the bottom of the trapezoidal shape connected to the handle, the top of the trapezoidal shape having the through hole, the side of the trapezoidal shape having the inlet, and a reservoir cavity formed inside the trapezoidal shape communicating with the through hole and the inlet. In other embodiments, the pipette tip may also be cylindrical, conical, or other shapes.

[0066] In some embodiments, at least one button located on the surface of the handheld portion is included for controlling the operating state of the ultrasonic device and adjusting the drive signal or power of the drive device of the ultrasonic device. In some embodiments, different buttons can be provided to control different functions. In some embodiments, a touch unit may also be included. In some embodiments, an LCD screen may also be provided to display the adjusted content or operating state. See also Figure 9 The diagram shown illustrates a circuit principle.

[0067] In some embodiments, a loop is also included on the handpiece away from the pipette tip.

[0068] In some embodiments, the device further includes a drive mechanism and related circuitry (such as a battery power supply circuit, circuitry connecting the aforementioned button, touch panel, or LCD screen, etc.) for the ultrasonic device built into the handheld unit. In other embodiments, the device further includes a drive mechanism for the ultrasonic device externally mounted on the handheld unit, and a cable passing through the handheld unit and electrically connecting the ultrasonic device and the drive mechanism.

[0069] In some embodiments, when the through-hole has a certain thickness, the through-hole can be provided with different shapes, such as... Figure 7 As shown in Figure A, the cross-section at the through-hole is cylindrical. In some embodiments, such as... Figure 7 As shown in Figure B, the cross-section at the through-hole is constricted, or narrowed, like a tapered hole. In some embodiments, such as... Figure 7 As shown in C, the cross-section at the through-hole is divergent, or flared, like a trumpet-shaped inverted cone. The through-hole has a certain thickness, creating a capillary effect, such as... Figure 7 As shown in the figures, the liquid in the storage cavity flows into the inside of the through hole. Due to the weight of the liquid and the surface tension of the liquid on the outside of the through hole, they reach equilibrium. The interfacial tension of the liquid at the through hole prevents the liquid in the storage cavity from flowing out through the through hole.

[0070] for Figure 7 As shown in B, when the through hole is constricted, the cross-section at the outer edge of the through hole is smaller than that at the inner edge of the through hole, thus relatively... Figure 7 As shown in A, the size of the ejected droplets can be reduced, such as... Figure 7 As shown in C, when the through-hole is flared, the liquid surface is located at the outer edge of the through-hole, making it easier for the liquid inside the through-hole to detach from the through-hole under the force of the acoustic beam. Therefore, relatively... Figure 7 As shown in Figure A, the ejected droplets will be larger. Therefore, the shape of the through-hole can be designed based on this, according to the required droplet size.

[0071] In other embodiments, in Figure 7The outer edge of the through hole in each figure can be further provided with annular protrusions to accommodate more liquid in the through hole based on capillary effect, thereby achieving control of the amount of sprayed droplets (i.e., droplet size) during spraying.

[0072] In some embodiments, the resolution (i.e., size) of the ejected droplets from a special ultrasonic device varies depending on the driving signal. Therefore, the driving device can generate a corresponding driving signal to drive the special ultrasonic device according to the required target droplet size. Different driving signals include, for example, driving signals with different powers, driving signals with different duty cycles, driving signals with different driving periods, and driving signals with different waveforms (such as triangular waves, square waves, sine waves, etc.).

[0073] In some embodiments, the size of the generated droplets is positively correlated with the power driving the ultrasonic device. This can be explained by the fact that a stronger driving power results in a stronger acoustic beam, leading to a greater amount of liquid exiting through the orifice, thus generating larger droplets and consequently, lower resolution of the ejected droplets.

[0074] In some embodiments, the size of the generated droplets is positively correlated with the duty cycle of the driving signal that drives the ultrasonic device. This can be explained by the fact that a larger duty cycle results in a stronger acoustic beam, leading to a greater amount of liquid exiting through the orifice, and thus a larger ejected droplet size.

[0075] In some embodiments, the size of the generated droplets is positively correlated with the size of the through-hole. This can be explained by the fact that the larger the through-hole size, the more liquid can be driven out of the through-hole, and therefore the larger the size of the ejected droplets.

[0076] In some embodiments, the size of the generated droplets is related to the physical properties of the liquid, such as viscosity and temperature. Generally, increasing the temperature can reduce the viscosity of the liquid, which is beneficial for the liquid to be ejected from the through-hole and form droplets. Therefore, a heating element can be placed close to the liquid storage cavity to regulate the temperature of the liquid in the storage cavity.

[0077] As can be seen above, whether droplets can be formed or the size of the formed droplets are related to the driving signal, the size of the through hole, the liquid properties (such as viscosity, mass or gravity), and the capillary force formed at the through hole (related to the liquid surface tension formed by the size and shape of the through hole). Therefore, when designing the size of the through hole, it is necessary to consider that the liquid will not leak from the through hole when the ultrasonic device is not working, and also to consider that the ultrasonic device can eject droplets from the through hole based on the above parameters when it is working. Furthermore, the size of the generated droplets can be controlled based on the above description.

[0078] In addition, the effects of various factors need to be considered. For example, when using higher power but a smaller drive signal duty cycle, it's equivalent to a momentary high power release of concentrated high-frequency energy, rapidly breaking through the surface tension of the liquid to form smaller droplets. Conversely, when using lower power but a larger drive signal duty cycle, it's equivalent to a longer period of low power, with the liquid surface being slowly impacted, resulting in larger droplets. The drive signal duty cycle and the overall power contribute to the energy generated in the droplet formation; therefore, these two values ​​are strongly correlated, as described in the subsequent sections. Figure 10 The example shown is an introduction to the experiment.

[0079] In some embodiments, the size of the generated droplets is related to the inherent resonant frequency of the ultrasonic device; the higher the resonant frequency, the smaller the size of the generated droplets.

[0080] In some embodiments, the frequency at which the droplets are formed is positively correlated with the frequency of the driving signal that drives the ultrasonic device.

[0081] In some embodiments, the liquid supplied to the reservoir can be ink, various biological reagents such as DNA solution, solutions containing microparticles or cells, or inorganic solutions.

[0082] In some embodiments, the ultrasonic device is driven with a first power cycle to generate an acoustic beam in a first liquid, and the magnitude of the first power should also be such that the generated acoustic beam can overcome the surface tension of the liquid at the through-hole to form droplets.

[0083] In some embodiments, when the ultrasonic device is an ultrasonic device, it can be a polygon, especially a polygon with an odd number of sides. For example, in one embodiment, it can be a regular pentagon or a scalene pentagon. In other embodiments, it can be an oval, triangular, elliptical, rhomboid, circular, semicircular, or any combination of shapes of any size polygon. Figure 8 A pentagonal ultrasonic device is shown, specifically an integrated acoustic resonator, and its dimensions compared to a coin are also shown. In some embodiments, the ultrasonic device may be an ultrasonic device operating in the range of 0.5 GHz to 50 GHz, preferably an ultrasonic device operating in the range of 1 GHz to 5 GHz, and more preferably an ultrasonic device operating in the range of 2 GHz to 2.5 GHz.

[0084] A second embodiment of this application provides a pipetting method using any of the handheld pipettes described in the first embodiment, the method comprising the following steps S10-S30:

[0085] S10: Inject liquid into the reservoir of the pipette through the inlet.

[0086] In some embodiments, the liquid to be transferred can be injected into the reservoir through the inlet using a syringe.

[0087] S20: Orient the pipette tip toward the target location.

[0088] S30: The ultrasonic device is put into operation, driving the liquid in the reservoir to generate an acoustic beam toward the through hole, at least a portion of the acoustic beam is ejected through the through hole to form droplets and reach the target position.

[0089] For example, pressing the first button on the handheld part can activate the ultrasonic device, putting it into operation. This operation can include an intermittent mode; for example, after pressing the first button once, the handheld pipette dispenses a drop, and then the ultrasonic device exits operation. When the first button is released and pressed again, the process repeats, dispensing another drop.

[0090] In some embodiments, the operating state may also include an intermittent mode, for example, when the first button is pressed and the handheld pipette is in the unreleased state, the handheld pipette will intermittently eject droplets continuously, wherein the interval time can be set, for example, a second button and a third button on the handpiece have corresponding interval time adjustment settings, which are used to decrease or increase the interval time adjustment respectively.

[0091] In some embodiments, a fourth and fifth button may also be provided, which can be used to adjust the increase or decrease of the drive signal power, that is, to adjust the size of each droplet.

[0092] In some embodiments, the button may be a physical button or a virtual button on the touch unit (such as a control displayed within the touch screen).

[0093] In some embodiments, the operating status of the ultrasonic device, the set operating mode, the aforementioned intermittent time, the drive cycle, and the power are also displayed via an LCD screen (e.g., a touch screen integrated with a touch unit). In some embodiments, the number of ejected droplets can also be displayed via a counting function. In some embodiments, the droplet size corresponding to different power levels is preset, and the size (or volume) of the currently ejected droplets is displayed according to the set power. In some embodiments, information such as the volume or mass of the ejected droplets can also be statistically displayed based on the number and size of the ejected droplets.

[0094] In some embodiments, the circuitry built into the handheld pipette may also include a wireless communication module, which can communicate with a wireless terminal (such as a laptop, mobile phone, PAD, computer with Wi-Fi, etc.) and realize the aforementioned settings and display functions on the wireless terminal based on the corresponding program on the wireless terminal.

[0095] For details of the above description, please refer to [link / reference]. Figure 9 The diagram illustrates a circuit principle. Figure 9 The first control unit and the control unit in the drive device can also be composed of a single chip with integrated functions. Figure 9 The button array in the middle can also be implemented by a touch unit.

[0096] In some embodiments, the size of the droplet can be changed by adjusting the drive signal or power of the drive device of the ultrasonic device. Adjusting the drive signal of the drive device of the ultrasonic device includes at least one of the following: adjusting the duty cycle of the drive signal, the duration of the continuous cycle of the drive signal, the waveform, etc., as specifically described in the first embodiment, and will not be repeated here.

[0097] In some embodiments, the method further includes: suspending the ultrasonic device and directing the pipette tip towards another target location. This facilitates the spraying of droplets to different target locations.

[0098] The above embodiments describe the handheld pipette of this application. It should be noted that the pipette described in this application includes pipettes in a broad sense, referring to any device that can move liquid from a first position to a second position. For example, it can spray liquid from a reservoir (first position) to a target position (second position), or it can draw liquid using another pipetting device (such as a syringe, pipette, conventional pipette, micropump, etc.) and inject it into the reservoir (first position) before spraying it to the target position (second position). In some embodiments, the other pipetting device can also be integrated with the handheld pipette of this application.

[0099] Furthermore, although this application is referred to as a handheld pipette, it is mainly to indicate that this application can be used by hand, but it does not limit this application to automatic pipettes. For example, the handheld pipette of this application can be assembled onto a robotic arm, robotic gripper, or support to achieve automatic pipetting.

[0100] In addition, this application also provides experimental diagrams to verify this application. For example... Figure 10 Figures A, B, C, and D show photographs of droplets and their diameter and volume data under different driving signals, including through-holes. Figure 7The A in the diagram has a cylindrical shape. The driving period of these driving signals is 20ms, but different duty cycles (i.e., different first-stage times) and different powers are used. The duty cycle (first-stage time) and power together form the energy required to drive the droplet generation. In this experiment, different duty cycles were set, and the power was gradually increased until droplets could be generated (this power can be considered as the minimum power required to generate droplets at the corresponding duty cycle). From this experiment, we can see... Figure 10 In the experiment, A represents the smallest droplet size, with a diameter of 16 μm and a volume of approximately 2.144 picoliters.

[0101] Figure 11 The analytical graph of the experimental results shown is Figure 10 Taking D as an example, then spray multiple droplets (corresponding to D). Figure 11 By distributing a certain number of ultrasonic droplets into the target volume of water and measuring the changes in fluorescence intensity and liquid concentration at the target location, the accuracy of the concentration gradient construction can be observed. The fluorescence intensity value is directly proportional to the number and concentration of the ejected droplets, and R... 2 =0.9997 proves the degree of matching with the theoretical value, demonstrating that the droplet uniformity and distribution accuracy of the embodiments of this application are high.

[0102] In the several embodiments provided in this application, it should be understood that the disclosed components, devices, and methods are not limited to the above embodiments and can be implemented in other ways. For example, the device embodiments described above are merely illustrative. For instance, the division of units is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the coupling or direct coupling or communication connection shown or discussed may be through some interfaces; the indirect coupling or communication connection between devices or units may be electrical, mechanical, or other forms.

[0103] The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the units can be selected to achieve the purpose of this embodiment according to actual needs.

[0104] Furthermore, the terms "first, second, third, etc." or similar terms such as module A, module B, and module C used in the specification and claims are only used to distinguish similar objects and do not represent a specific ordering of objects. It is understood that, where permissible, a specific order or sequence may be interchanged so that the embodiments of this application described herein can be implemented in an order other than that illustrated or described herein.

[0105] In the above description, the labels of the steps involved, such as S10, S20, etc., do not mean that the steps will necessarily be executed. The order of the steps can be interchanged or executed simultaneously if permitted.

[0106] The term "comprising" as used in the specification and claims should not be construed as limiting itself to what follows; it does not exclude other elements or steps. Therefore, it should be interpreted as specifying the presence of the mentioned feature, integral, step, or component, but does not exclude the presence or addition of one or more other features, integrals, steps, or components, or groups thereof. Thus, the statement "device comprising means A and B" should not be limited to a device consisting solely of components A and B.

[0107] The terms "an embodiment" or "an embodiment" as used in this specification mean that a particular feature, structure, or characteristic described in conjunction with that embodiment is included in at least one embodiment of this application. Therefore, the terms "in one embodiment" or "in an embodiment" appearing throughout this specification do not necessarily refer to the same embodiment, but may refer to the same embodiment. Furthermore, in one or more embodiments, the particular features, structures, or characteristics can be combined in any suitable manner, as will be apparent to those skilled in the art from this disclosure.

[0108] Note that the above are merely preferred embodiments and the technical principles employed in this application. Those skilled in the art will understand that this application is not limited to the specific embodiments described herein, and various obvious changes, readjustments, and substitutions can be made without departing from the scope of protection of this application. Therefore, although this application has been described in detail through the above embodiments, this application is not limited to the above embodiments, and may include many other equivalent embodiments without departing from the concept of this application, all of which fall within the scope of protection of this application.

Claims

1. A handheld pipette, characterized in that, include: The handheld part and the pipette tip located at one end of the handheld part, wherein the pipette tip forms a reservoir for containing liquid; The liquid storage chamber has an outlet and an inlet, and an ultrasonic device is provided inside the liquid storage chamber or on the inner wall of the liquid storage chamber; The liquid outlet includes a through hole, the size of which is limited so that the liquid in the storage chamber does not flow out of the through hole when the ultrasonic device is not working; When the ultrasonic device is in operation, it drives the liquid in the reservoir to generate an acoustic beam toward the through hole, and at least a portion of the acoustic beam is ejected through the through hole to form droplets.

2. The handheld pipette according to claim 1, characterized in that, The distance between the ultrasonic device and the through hole is set so that the energy of the ultrasonic device can be completely attenuated and converted into the energy of droplet ejection.

3. The handheld pipette according to any one of claims 1-2, characterized in that, The ultrasonic device is positioned directly opposite the through hole.

4. The handheld pipette according to any one of claims 1-3, characterized in that, The through holes are arranged in an array of multiple holes, and the ultrasonic devices are arranged in a corresponding array of multiple holes.

5. The handheld pipette according to any one of claims 1-4, characterized in that, The pipette tip is generally trapezoidal in shape. The bottom of the trapezoidal shape is connected to the handheld part, the top of the trapezoidal shape has the through hole, the side of the trapezoidal shape has the liquid inlet, and the interior of the trapezoidal shape forms the liquid storage cavity that connects the through hole and the liquid inlet.

6. The handheld pipette according to any one of claims 1-5, characterized in that, The height of the liquid inlet is higher than that of the ultrasonic device, so that the space between the ultrasonic device and the through hole is filled with the liquid.

7. The handheld pipette according to any one of claims 1-6, characterized in that, It also includes at least one of the following: At least one button located on the surface of the handheld part is used to control the working state of the ultrasonic device and adjust the drive signal or power of the drive device of the ultrasonic device. The lug is located on the handpiece away from the pipette tip; A drive device for the ultrasonic device built into the handheld part; or, a drive device for the ultrasonic device externally placed in the handheld part, and a cable passing through the handheld part and electrically connected to the ultrasonic device and the drive device.

8. A pipetting method, characterized in that, Using the handheld pipette according to any one of claims 1-7, the method comprises: Liquid is injected into the reservoir of the pipette through the inlet; Orient the pipette tip toward the target location; The ultrasonic device is put into operation, driving the liquid in the reservoir to generate an acoustic beam toward the through hole. At least a portion of the acoustic beam is ejected through the through hole to form droplets and reach the target position.

9. The pipetting method according to claim 8, characterized in that, Also includes: Adjusting the drive signal or power of the drive device of the ultrasonic device can change the size of the droplet.

10. The pipetting method according to claim 9, characterized in that, The drive signal of the drive device for adjusting the ultrasonic device includes at least one of the following: Adjust the duty cycle, duration of continuous periods, and waveform of the drive signal.

Images